1. Field of the Invention
The subject invention relates to a process for eliminating N-nitrosamines from N-nitrosamine-containing compositions. More specifically, the subject invention relates to the removal of N-nitrosamine impurities which are typically found in intermediates and finished products in the dye, pigment, pharmaceutical and herbicide industries.
2. Description of the Prior Art
N-nitrosamines are found in a wide variety of products in amounts ranging from trace amounts barely detectable by the most modern equipment to fairly large quantities, approaching 30 percent by weight in some instances. Natural products such as Scotch whiskey and beer have also been shown to contain small quantities of these substances.
The formation of N-nitrosamines in the many products in which they occur apparently takes place by a variety of mechanisms, at least some of which are still unknown. ln the manufacture of many dyes and pesticides, however, it is believed that trace amounts of nitrosating agents derived from prior nitration processes in nitro-substituted intermediates react subsequently with amines or substituted amines to form the corresponding N-substituted-N-nitrosamines. For example, in the manufacture of trifluralin herbicide, N,N-dipropylamine is reacted with 1-chloro-2,6-dinitro-4-(trifluoromethyl)benzene. During the process N-nitroso-N,N-dipropylamine is formed as an impurity in amounts up to several hundred parts per million (ppm).
Many N-nitrosamines are highly toxic. N,N-dimethylnitrosamine, for example, has a LD.sub.50 of only 10 mg/Kg. Of greater significance than their toxicity, however, are potential carcinogenic, mutagenic, and teratogenic effects. Many, if not most N-nitrosamines, are classified as animal carcinogens by OSHA, for example.
Because of the aforementioned deleterious health-related effects, stringent limitations have been placed upon the permissible amounts of N-nitrosamine impurities in consumer products such as cosmetics, pharmaceuticals, pesticides, dyes and pigments. Because of the exceptionally low allowable limits for N-nitrosamine impurities in these products, their virtually complete removal or destruction has often been problematic.
One conceivable method of eliminating N-nitrosamines from products is to prevent their formation in the first place. Elimination of nitrosating agents as a means of decreasing N-nitrosamine formation is disclosed in U.S. Pat. No. 4,120,905, for example, where a 1-chloro-2,6-dinitro-4-(trifluoromethyl)benzene intermediate is stripped of nitrosating agents with the aid of a non-reactive gas at a temperature of 50.degree. C. to 100.degree. C. in an aqueous alkaline solution. Unfortunately, a two-step treatment with large quantities of solution are required to achieve levels of less than ca. 10 ppm of N-nitrosamine following reacting of the "nitrosating agent free" intermediate with N,N-dipropylamine. This residual N-nitrosamine concentration is still too high for commercial products. Furthermore, the disposal of large quantities of aqueous alkali is necessitated by this process.
Perhaps the oldest and most effective method of N-nitrosamine destruction involves heating with concentrated hydrochloric acid. This process, for example, was well described by Renouf in Berichte 13, pp. 2169-74 (1880), and, in conjunction with the use of anhydrous hydrogen chloride, is the subject of U.S. Pat. No. 4,226,789. According to the process of U.S. Pat. No. 4,226,789, N-nitrosamines may be removed from dinitroaniline herbicides by heating with concentrated hydrochloric acid. Generally, 10 percent to 30 weight percent of concentrated hydrochloric acid relative to the weight of N-nitrosamine-containing product is used where the amount of N-nitrosamine impurity is relatively small (&lt;1000 ppm). The mixture is agitated for a time period of from 0.25 hour to several hours at a temperature above the melting point of the product, generally from 70.degree. C. to 90.degree. C. The residual N-nitrosamine level is generally less than 1 ppm utilizing this method.
Unfortunately, the large quantities of concentrated hydrochloric acid utilized in the process of U.S. Pat. No. 4,226,789 and the attendant problems of equipment corrosion, neutralization and washing of the product, and disposal of large quantities of acid waste render this process less than ideal.
The process of U.S. Pat. No. 4,185,035 is similar to that of U.S. Pat. No. 4,226,789 except that inorganic halides such as PCl.sub.3, PBr.sub.3, POCl.sub.3, TiCl.sub.4, and SO.sub.2 Cl.sub.2, are utilized in place of hydrochloric acid. The inorganic halides used in this process, however, are difficult to handle, volatile, corrosive, and toxic. Moreover, some of the inorganic halides, especially those containing sulfur or heavy metals give rise to toxic by-products which, in turn, can cause a waste disposal problem. Furthermore, the use of these inorganic halides does not appear to reduce the N-nitrosamine levels to those obtainable with concentrated hydrochloric acid.
U.S. Pat. No. 4,134,917 describes a process for the denitrosation of organic N-nitrosamines by the addition of an aldehyde or ketone In the presence of strong acid. This process is capable of eliminating large quantities of N-nitrosamines, but requires considerable quantities of concentrated hydrochloric acid as does the process of U.S. Pat. No. 4,426,789. Furthermore, the N-nitrosamine impurity levels, while considerably lower than their initial values, are much too high for applications such as food dyes, cosmetics, and herbicides. Residual levels of N-nitrosamines of 0.01 percent, or 100 ppm, are typical, for example, with the best results reported to be ca. 10 ppm.